tert-butyl 3-(3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate | 1403775-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 3-(3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate
• 英文别名: Tert-butyl 3-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate；tert-butyl 3-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate
• CAS: 1403775-96-1
• 化学式: C₁₆H₁₈FN₃O₃
• 分子量: 319.336
• InChiKey: OMKVEXILWSJNLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  68.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate 在 盐酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 [3-[3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-(2-methylcyclohexyl)methanone
  参考文献：
  名称：

  Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators

  摘要：

  A novel series of aryl azetidinyl oxadiazoles are identified as mGluR5 positive allosteric modulators (PAMs) with improved physico-chemical properties. N-substituted cyclohexyl and exo-norbornyl carboxamides, and carbamate analogs of azetidines are moderate to potent mGluR5 PAMs. The aryl, lower alkyl carboxamides analogs and sulfonamide analogs of azetidines are moderate mGluR5 negative allosteric modulators (NAMs). In the aryl oxadiazole moiety, substituents such as fluoro, chloro and methyl are well tolerated at the meta position while para substituents led to either inactive compounds or NAMs. A tight pharmacophore and subtle 'PAM to NAM switching' with close analogs makes the optimization of the series extremely challenging. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.044
• 作为产物：
  描述：

  1-N-Boc-3-吖丁啶羧酸 生成 tert-butyl 3-(3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate
  参考文献：
  名称：

  Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators

  摘要：

  A novel series of aryl azetidinyl oxadiazoles are identified as mGluR5 positive allosteric modulators (PAMs) with improved physico-chemical properties. N-substituted cyclohexyl and exo-norbornyl carboxamides, and carbamate analogs of azetidines are moderate to potent mGluR5 PAMs. The aryl, lower alkyl carboxamides analogs and sulfonamide analogs of azetidines are moderate mGluR5 negative allosteric modulators (NAMs). In the aryl oxadiazole moiety, substituents such as fluoro, chloro and methyl are well tolerated at the meta position while para substituents led to either inactive compounds or NAMs. A tight pharmacophore and subtle 'PAM to NAM switching' with close analogs makes the optimization of the series extremely challenging. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.044

文献信息

• In Vitro and in Vivo Evaluation of ¹¹C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies
  作者：Ran Cheng、Wakana Mori、Longle Ma、Mireille Alhouayek、Akiko Hatori、Yiding Zhang、Daisuke Ogasawara、Gengyang Yuan、Zhen Chen、Xiaofei Zhang、Hang Shi、Tomoteru Yamasaki、Lin Xie、Katsushi Kumata、Masayuki Fujinaga、Yuji Nagai、Takafumi Minamimoto、Mona Svensson、Lu Wang、Yunfei Du、Mary Jo Ondrechen、Neil Vasdev、Benjamin F. Cravatt、Christopher Fowler、Ming-Rong Zhang、Steven H. Liang

  DOI：10.1021/acs.jmedchem.7b01400

  日期：2018.3.22

  Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including C-11-carbonylation and spirocyclic iodonium ylide (SCIDY) radio fluorination. The lead compound [C-11]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.